Gunn, John
John GunnPh.D. Associate Professor
Department of Molecular Virology, Immunology and Medical Genetics Joint Appointment Department of Internal Medicine Research Summary: Dr. Gunn's laboratory is primarily interested in the molecular mechanisms used by Salmonella spp. to survive harsh conditions it encounters within the human host. Salmonellae encounter numerous anatomic sites during infection, including the inhospitable environment of the macrophage phagosome, where they are able to survive and replicate. Present within host phagocytes (and at mucosal surfaces) are a potent group of cytotoxic agents, antimicrobial peptides (AP). The PmrA-PmrB two-component regulatory system is activated when Salmonella are within host macrophages, and is necessary for resistance to AP, which involves modifications of the LPS that decrease peptide binding. He is focused on studies of the PmrA-PmrB regulon, including the identification and characterization of PmrA-PmrB regulated genes necessary for AP resistance and LPS modification, and the determination of the role of PmrA-PmrB mediated LPS modifications in Salmonella virulence. Bile salts are detergents made by the liver that are stored in the gallbladder and released into the intestine to aid digestion. Salmonella spp. come in contact with bile salts in the intestine, and in the chronic carrier state, within the gallbladder. Salmonella is able to resist the action of bile and respond to escalating bile concentrations by increasing mechanisms of resistance. He is currently trying to understand: (1) how Salmonella is able to sense bile, (2) what mechanisms of bile resistance exist in Salmonella, and (3) how biofilm formation on gallstones may aid in development of the carrier state. Finally, Dr. Gunn's laboratory is interested in pathogenesis and intramacrophage survival of the Category A biodefense agent, Francisella tularensis. This work involves the characterization of regulatory factors required for the activation of virulence genes, and the study of Francisella acid phosphatases that are involved in intramacrophage survival and virulence. The identification of virulence genes may lead to the development of live-attenuated vaccines against tularemia. Selected Publications: Prouty, A.M. and J.S. Gunn. 2002. Biofilm Formation and Interaction with the Surfaces of Gallstones by Salmonella spp.. Infect. Immun. 70:2640-2649. Tamayo, R., S.S. Ryan, A.J. McCoy, and J.S. Gunn. 2002. Identification and genetic characterization of PmrA-regulated genes and genes involved in polymyxin B resistance in Salmonella enterica Serovar Typhimurium. Infect. Immun. 70:6770-6678. Tamayo, R., B. Choudhury, A. Septer, M. Merighi, R. Carlson and J. S. Gunn. 2005. Identification of cptA, a PmrA-Regulated Locus Required for Phosphoethanolamine Modification of the Salmonella enterica serovar Typhimurium Lipopolysaccharide Core. J. Bacteriol. 187:3391-3399. Merighi, M., C.D. Ellermeier, J. M. Slauch and J. S. Gunn. 2005. Resolvase-IVET Analysis of the Salmonella enterica sv. Typhimurium PhoP and PmrA regulons in BALB/c mice. J. Bacteriol.187:7407-7416. Gavrilin MA, I. Bouakl, N. Knatz, M. Duncan, M.W. Hall, J.S. Gunn and M.D. Wewers. 2006. Internalization and phagosome escape required for live Francisella to induce human monocyte IL-1ß? processing and release. PNAS 103:141-146. Balagopal, A., A. Shearer MacFarlane, N. Mohapatra, S. Soni, J.S. Gunn and L.S. Schlesinger. 2006. Characterization of the receptor-ligand pathways important for entry and survival of Francisella novicida and the live vaccine strain (LVS) of F. tularensis in human macrophages. Infect. Immun. 74:5114-5125. K.V. L. Parsa , L. P. Ganesan , M.V. S. Rajaram , M. A. Gavrilin , A. Balagopal , N. P. Mohapatra, M. D. Wewers, L. S. Schlesinger, J. S. Gunn, S.Tridandapani . 2006. Macrophage pro-inflammatory response to Francisella novicida infection is regulated by the SH2 domain-containing inositol 5’ phosphatase SHIP. PLoS Pathogens, 7:e71, p681-690. Mohaptara, N., A. Balagopal, L. S. Schlesinger, and J. S. Gunn. 2007. AcpA, an acid phosphatase involved in Francisella tularensis virulence. Infect. Immun.. 75:390-6.
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